Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

Siew Kee Low, Atsushi Takahashi, Yusuke Ebana, Kouichi Ozaki, Ingrid E. Christophersen, Patrick T. Ellinor, Soichi Ogishima, Masayuki Yamamoto, Mamoru Satoh, Makoto Sasaki, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Keitaro Tanaka, Mariko Naito, Kenji Wakai, Hideo Tanaka, Tetsushi Furukawa, Michiaki Kubo, Kaoru Ito & 2 others Yoichiro Kamatani, Toshihiro Tanaka

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To investigate genetic loci associated with atrial fibrillation in the Japanese population, we performed a genome-wide association study (GWAS) that included 8,180 atrial fibrillation cases and 28,612 controls with follow-up in an additional 3,120 cases and 125,064 controls. We replicated previously reported loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2, NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated with atrial fibrillation in the Japanese population after comparing our data to those from individuals of European ancestry, suggesting that there might be different genetic factors affecting susceptibility across ancestry groups. Our study discovered variants in the HAND2, KCND3 and NEBL genes, which are relevant to atrial fibrillation susceptibility. The involvement of PPFIA4 and SH3PXD2A in axon guidance also suggested a role in disease pathogenesis. Our findings may contribute to a better understanding of atrial fibrillation susceptibility and pathogenesis.

Original languageEnglish
Pages (from-to)953-958
Number of pages6
JournalNature Genetics
Volume49
Issue number6
DOIs
Publication statusPublished - 01-06-2017

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Genetic Loci
Atrial Fibrillation
Population
Genome-Wide Association Study
Genes
Cardiac Arrhythmias
Stroke

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Low, S. K., Takahashi, A., Ebana, Y., Ozaki, K., Christophersen, I. E., Ellinor, P. T., ... Tanaka, T. (2017). Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nature Genetics, 49(6), 953-958. https://doi.org/10.1038/ng.3842
Low, Siew Kee ; Takahashi, Atsushi ; Ebana, Yusuke ; Ozaki, Kouichi ; Christophersen, Ingrid E. ; Ellinor, Patrick T. ; Ogishima, Soichi ; Yamamoto, Masayuki ; Satoh, Mamoru ; Sasaki, Makoto ; Yamaji, Taiki ; Iwasaki, Motoki ; Tsugane, Shoichiro ; Tanaka, Keitaro ; Naito, Mariko ; Wakai, Kenji ; Tanaka, Hideo ; Furukawa, Tetsushi ; Kubo, Michiaki ; Ito, Kaoru ; Kamatani, Yoichiro ; Tanaka, Toshihiro. / Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. In: Nature Genetics. 2017 ; Vol. 49, No. 6. pp. 953-958.
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Low, SK, Takahashi, A, Ebana, Y, Ozaki, K, Christophersen, IE, Ellinor, PT, Ogishima, S, Yamamoto, M, Satoh, M, Sasaki, M, Yamaji, T, Iwasaki, M, Tsugane, S, Tanaka, K, Naito, M, Wakai, K, Tanaka, H, Furukawa, T, Kubo, M, Ito, K, Kamatani, Y & Tanaka, T 2017, 'Identification of six new genetic loci associated with atrial fibrillation in the Japanese population', Nature Genetics, vol. 49, no. 6, pp. 953-958. https://doi.org/10.1038/ng.3842

Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. / Low, Siew Kee; Takahashi, Atsushi; Ebana, Yusuke; Ozaki, Kouichi; Christophersen, Ingrid E.; Ellinor, Patrick T.; Ogishima, Soichi; Yamamoto, Masayuki; Satoh, Mamoru; Sasaki, Makoto; Yamaji, Taiki; Iwasaki, Motoki; Tsugane, Shoichiro; Tanaka, Keitaro; Naito, Mariko; Wakai, Kenji; Tanaka, Hideo; Furukawa, Tetsushi; Kubo, Michiaki; Ito, Kaoru; Kamatani, Yoichiro; Tanaka, Toshihiro.

In: Nature Genetics, Vol. 49, No. 6, 01.06.2017, p. 953-958.

Research output: Contribution to journalArticle

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T1 - Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

AU - Low, Siew Kee

AU - Takahashi, Atsushi

AU - Ebana, Yusuke

AU - Ozaki, Kouichi

AU - Christophersen, Ingrid E.

AU - Ellinor, Patrick T.

AU - Ogishima, Soichi

AU - Yamamoto, Masayuki

AU - Satoh, Mamoru

AU - Sasaki, Makoto

AU - Yamaji, Taiki

AU - Iwasaki, Motoki

AU - Tsugane, Shoichiro

AU - Tanaka, Keitaro

AU - Naito, Mariko

AU - Wakai, Kenji

AU - Tanaka, Hideo

AU - Furukawa, Tetsushi

AU - Kubo, Michiaki

AU - Ito, Kaoru

AU - Kamatani, Yoichiro

AU - Tanaka, Toshihiro

PY - 2017/6/1

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N2 - Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To investigate genetic loci associated with atrial fibrillation in the Japanese population, we performed a genome-wide association study (GWAS) that included 8,180 atrial fibrillation cases and 28,612 controls with follow-up in an additional 3,120 cases and 125,064 controls. We replicated previously reported loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2, NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated with atrial fibrillation in the Japanese population after comparing our data to those from individuals of European ancestry, suggesting that there might be different genetic factors affecting susceptibility across ancestry groups. Our study discovered variants in the HAND2, KCND3 and NEBL genes, which are relevant to atrial fibrillation susceptibility. The involvement of PPFIA4 and SH3PXD2A in axon guidance also suggested a role in disease pathogenesis. Our findings may contribute to a better understanding of atrial fibrillation susceptibility and pathogenesis.

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Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT et al. Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nature Genetics. 2017 Jun 1;49(6):953-958. https://doi.org/10.1038/ng.3842